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Instantaneous Parameter Estimation in Cardiovascular Time Series by Harmonic and Time-Frequency Analysis
Alessandro Monti3 , Claire Mdigue, and Laurence Mangin
AbstractTime-frequency distributions, such as smoothed pseudo WignerVille distribution (SPWVD), complex demodulation (CDM), and provide useful time-varying spectral parameter estimators. However, each of these methods has limitations that a joint utilization could largely reduce, due to their interesting complementary features. The aim of this paper is to validate the joint SPWVDCDM method on synthetic and real cardiovascular time series with normal and reduced variability such as in autonomic blockade or autonomic deficiency. We propose two indexes related to the noise present in the signal and to the dispersion of the power spectrum in order to validate instantaneous parameter estimation. In the low-frequency band, the interpretation of the instantaneous frequency and phase of cardiovascular time-series should be discarded in many real-life situations. Conversely, in the high frequency band, under paced breathing, the reliability of the instantaneous parameters is demonstrated even in conditions of reduced cardiovascular variability. Index TermsAutonomic nervous system, blood pressure variability, complex demodulation, heart rate variability, WignerVille distribution.

(IF) of the oscillatory components present in the cardiovascular time series [10], [11], [13], [19], [23][25]. A comparison between the time frequency and the local harmonic methods on real cardiovascular time series has never been made. Both of them present limitations that a joint utilization could largely reduce: the CDM is suitable to assess the instantaneous phase (IPh) relationship between two oscillations; the SPWVD is suitable to assess the reliability of IF and IPh estimate. The aim of this paper is to validate the joint SPWVDCDM method on simulations and physiological experiments. We propose two indexes related to the noise present in the signal and to the dispersion of the power spectrum in order to detect and quantify the time changes in the cardiovascular variability, even when this variability is greatly reduced, such as in autonomic blockade and autonomic nervous system deficiency.

II. METHODS A. Instantaneous Spectral Parameters The parameters are the IAmp and IF of the HF and LF components of the cardiovascular time series, and the instantaneous ) between the HF component and the respiratory phase ( signal. IAmp provides information on the relative contribution provides informaof an oscillation to the signal variability. tion on the rhythm of this oscillation. The definition of the of a signal implicitly assumes that at each instant the signal is merely monocomponent [5], [6]. We will demonstrate that even for signals with few, a priori known, well-separated components, such as cardiovascular time series, a prefiltering could split the different spectral components allowing the estimate provides information on the synchronizafor each of them. tion between the oscillations in the two signals and 1 : 1 coupling value over time. is evidenced by a constant B. CDM Method

I. INTRODUCTION HE analysis of the beat-to-beat variability of cardiovascular time series has been widely used as a noninvasive approach to study the autonomic nervous system activity. The power spectrum of these fluctuations, obtained by standard spectral analysis [1], [14], evidences the presence of two principal peaks, in the low-frequency (LF) and high-frequency (HF) band. Spectral analysis assumes stationarity of the data and provides frequency domain parameters averaged over a given period [23]. On the other hand, time-frequency distributions, such as the smoothed pseudo WignerVille distribution (SPWVD), and local harmonic analysis, the complex demodulation (CDM), provide useful time-varying spectral parameter estimators. The SPWVD and CDM methods have already been used separately to estimate time-dependent changes in the instantaneous amplitude (IAmp) and instantaneous frequency
Manuscript received December 3, 2001; revised July 23, 2002. The work of L. Mangin was supported by the DRC Assistance Publique-Hopitaux de Paris and by the Research Foundation Simone and Cino Del Duca, Paris, France. Asterisk indicates corresponding author. A. Monti is with the French National Institute for Research in Computer Science and Control (INRIA), Project SOSSA, Bt. 12, BP 105, Le Chesnay 78153, France (e-mail: alessandro.monti@inria.fr). C. Mdigue is with the French National Institute for Research in Computer Science and Control (INRIA), Le Chesnay 78153, France. L. Mangin is with the Pneumology and Intensive Care Unit Department, UPRES 2397 Groupe Hospitalier Piti Salptrire, Paris, France. Digital Object Identifier 10.1109/TBME.2002.805478

be a narrow band with 1) Properties: Let the real signal a center frequency ( ) larger than the bandwidth of its spectra. This constraint is necessary and sufficient to extract the enve[12]. Since any signal has enlope and phase functions of , a reliable bandergy outside the frequency of interest pass filter (such as a windowed finite impulse response) has to be applied before the extraction of the envelope and phase by includes a component with an CDM. Therefore, the signal which changes slowly around a frequency actual frequency

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of within the range . Thus, theorem [7] and can be written as

satisfies Bedrosians

with

(1)

and are the instantaneous amplitude and phase where is the of the component of interest, slowly modified, and residual time series including all other components and noises such as continuous component and trends. The difference beand is expressed as the slope tween the actual frequency versus time of (2)

effects on the and IAmp estimate and gives better time res, the olution in noisy environments. Finally, setting represents the real phase relationship between respiratory and high frequency cardiovascular activity. 2) Limitations of the CDM Method: The CDM method is based on the assumption that only the component of interest is ) otherwise present within the defined frequency band ( the algorithm would yield unpredictable and noisy related and values. Until now, the only criterion of reliability was based on an a priori fixed threshold for the IAmp [11]. We will show that noise and interactions between the HF and LF comand estimate, and that the ponents really do affect the CDM method alone is not able to estimate these influences. C. SPWVD Method

The aim of the analysis is to extract an approximation of and as function of time. Using the Hilbert transform ( ), Gabors complex analog of is (3) is Gabors complex signal of [9]. Then, let where be the signal obtained by shifting all the frequencies in by (4) is around The peak of interest in the power spectrum of (within ). A leftward shift of all frequencies moves this ) in the power spectrum of . peak around zero (within excludes Thus, a low-pass filter with a corner frequency of all components except the component of interest. The resulting signal is (5) Therefore, the instantaneous amplitude, phase, and frequency functions are given by

1) Properties: The power spectral density is a function that represents the energy of a signal in the time-frequency domain. A satisfactory and unequivocal definition of time-varying spectrum does not exist [8]. A time-frequency distribution widely used is the WignerVille distribution [4], [8], [17], [23]. It is always real-valued, has a very good time and frequency resolution preserving time and frequency shifts. This distribution satisfies the marginal properties: the energy spectral density and the instantaneous power can be obtained as a marginal distribution of the WignerVille distribution [8], [17], [23]. Its major limitation is that two components of different frequency interfere, producing oscillatory cross terms in their middle, with negative values [17]. This could be reduced by a time averaging of the spectra [8], [17], [23]. The SPWVD is defined as

(7) and are the window sizes of and respecwhere weights the input time-series and tively, the window averages the instantaneous spectrum. In the the window SPWVD a tradeoff is required between the time-frequency resolution and the suppression of the cross term: smoothing in time and/or in frequency by reduces the time resolution by and/or the frequency resolution [23]. Even if the marginal properties are no longer strictly valid and the time resolution re, [23]), we can use the duced (depending on the duration of ) and SPWVD to estimate both the instantaneous power ( frequency ( ) of the signal by the first two-order moments of the distribution

(6) in (2), and the cutoff By changing the central frequency, in (1), it is possible to repeat this procedure, anfrequency, alyzing all oscillations actually present in a multicomponent signal. The classical CDM method is applied with fixed HF and LF parameters [10], [11], [24], [25], corresponding to the frequency bands defined by the task force [26]. The width of these bands imposes a large cutoff frequency ( ) to the low-pass filter. By applying the CDM method to the respiratory signal, one can estimate the actual breathing rate ( ) by the parameter. Only estimate was used in the cardiovascular HF band recently, a and lowering the cutoff frequency analysis, fixing ( ) of the band-pass filter [18], [27]. This largely reduces noise

(8) To compare the SPWVD and CDM methods the instantaneous ) was converted to the instantaneous amplitude as power ( follows: (9) where is a constant dependent on the filter properties.

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2) Two Proposed Indexes: Instantaneous Noise Estimation and SPWVD Dispersion: a) Instantaneous Noise Estimation: Given an ideal distribution which describes the energy density of a signal simultaneously in time and frequency, we could easily define an index to estimate the noise in a signal. If the oscillation of interest lies within an a priori known frequency band (FB) and the noise outside, we could prefilter the signal and estimate the relative contribution of the noise to its instantaneous power as

values could reveal that a large FB contains all the energy of the widely spread spectrum of the signal (case of LF band and of HF band during spontaneous breathing). Conversely, high and low values could reveal that the spectral peak is outand , jointly, are effective tools to side FB. Hence, quantitatively describe the instantaneous spectral composition and dispersion of a signal. between 3) Limitations of the SPWVD Method: The and could be calculated as two monocomponent signals follows: (14)

(10) is the ideal distribution of the signal where . The noise-to-signal power ratio (NSR) takes its value in [0, 1], 0 when all the energy of the signal is inside the FB region and 1 in the opposite situation. Such an ideal distribution estimated by the does not exist [8], and in particular, the SPWVD can take negative values. Nevertheless an estimation of the noise present in the signal could be carried out as follows (11) The SPWVD of a monocomponent signal, linearly modulated is in frequency is concentrated in one point [4], [8] and equal to 0 if this point belongs to the FB region, 1, otherwise. Oscillating cross-terms and negative regions imply that approximates the NSR index; an effective signal prefiltering and estimaWVD smoothing become very important for the is, the more reliable tion. We will show that the smaller and are. b) Instantaneous SPWVD Dispersion: In order to estimate the spread in frequency of the SPWVD, we could use a classical definition of variance which, interestingly, corresponds to the third moment of a distribution (12) could take negative values, we defined the following As index for the estimation of the dispersion of the SPWVD: (13) is always positive and equal to the if and only if The SPWVD is positive. The SPWVD of a monocomponent signal, linearly modulated in frequency is concentrated in one point [4], is equal to 0. For large values, [8] and, hence, the estimates are meaningless as the signal is not monocomponent. is, the more reliable and We will show that the smaller are. estimates c) Complementarity of the Two Indexes: the ratio between the energy of the signal in an a priori defined esfrequency band (FB) and the total energy of the signal. timates the spreading of the SPWVD in the frequency direction, and high without a frequency band definition. Low

and are the instantaneous frequency of the where and , respectively. two oscillations and estimate by (8), but is SPWVD allows . Therefore, it can provide only not suitable to estimate phase-shift between two monocomponent signals, integral term between them. in (14), but not the absolute phase D. Joint SPWVDCDM Method 1) Signal Processing Scheme: Both the SPWVD and the CDM methods present limitations that a joint utilization could largely reduce: CDM is well-suited for assessing the relationship between two oscillations; SPWVD is suitable for and estimate. Fig. 1 assessing the reliability of the shows the different steps of the joint SPWVDCDM method applied to HF analysis. First of all, cardiovascular time-series are prefiltered in the a priori defined HF or LF band to reduce noise. Second, SPWVD allows the detection of reliable and estimate periods corresponding to low values for and parameters. During these periods, CDM is and values while SPWVD provides applied, providing values. IAmp analysis does not need a preliminary period selection and in fact, it can be obtained directly by the CDM or SPWVD method. We will show that the two methods provide a very close IAmp estimate in both the HF and LF band, whereas and values imply close estimates by very low the two methods. 2) Evaluation of the Joint SPWVDCDM Method: a) Evaluation of the Instantaneous Spectral Parameters on Synthetic Signals: We compared the estimated parameters to the theoretical ones on several RR-like series testing the ability and to detect unreliable and estimates. of The most representative time-series are the following:

(15)

[ms] represents a RR-like series sampled at 4-Hz and 1000 ms is its mean value. is the time varying amplitude in the HF band: IAmp ms s, ms for s and ms for s and linearly interpolated between, see Fig. 2. and are sinusoidally modulated LF and HF components, around 0.09 Hz with amplitude 0.01 Hz

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Fig. 1. The different steps of the joint SPWVDCDM method for HF analysis. The demodulating frequency of the cardiovascular time-series f is fixed to the actual BR, whereas the demodulating frequency of the respiratory time-series f is an a priori fixed value corresponding to a physiological breathing frequency could be fixed to an a priori low frequency value. (0.25 Hz) or to the imposed external rhythm. For LF analysis f

Fig. 2. The two synthetic RR-like series, x (k ) on the top, x (k ) on the bottom, defined by (15) and (16).

and period 150 s for LF, around 0.25 Hz with amplitude 0.01 Hz and period 80 s for HF (see Fig. 2 for the HF component and, for software implementation, see fmsin.m function in [22]). [ms]. is a white Gaussian noise with mean 0 s and standard deviation of 0.5 ms.

s [ms].

(16)

is a white Gaussian noise with mean 0 s and standard deviation of 4 ms. time-series, a greater amplitude and In the standard deviation produced a larger noise contribution to signal variability. These time series concentrate their energy in the well-defined HF and LF regions of the plane. They simulate time-dependent changes in the frequency location and amplitude of the respiratory sinus arrhythmia of an RR series during a

0.25 Hz paced breathing test (Fig. 2). They simulate typical real cardiovascular time series in normal but also in reduced variability condition usually evidenced in autonomic deficiency. b) Evaluation of the Instantaneous Spectral Parameters on Real Cardiovascular Time Series: ECG, blood pressure (Finapres), and respiratory (Respitrace Systems) signals were recorded at 500 Hz by dedicated software (Acknowledge III, BIOPAC systems, USA). Signal processing was performed with LARY_CR, software developed at INRIA, in the scientific environment SCICOS-SCILAB [21], [20]. Rhythm detection was applied to raw cardiovascular signals: for RR, an adaptative threshold was applied to the derivative ECG; systolic (SBP) and diastolic (DBP) blood pressure were determined with a variant of Pans algorithm, as described in [15] and [19]. Cardiovascular time series were resampled at 4 Hz. The joint SPWVDCDM method was applied on several testing conditions to evaluate the influence of different parameters (HF band definition, BR, cardiovascular variability) on the estimation of the instantaneous spectral parameters. 1) During spontaneous breathing in normal subjects Spontaneous breathing requires a wide HF band because of large changes in . The subjects were recorded over a period of five minutes in quiet conditions. 2) During paced breathing in normal and CHF subjects Paced breathing allows a narrow HF band definition centered around the actual breathing rate. Breathing activity was paced at 0.25 Hz and 0.15 Hz. The CHF subjects present a reduced variability. Subjects were recorded over two periods of five minutes, . corresponding to 0.25 Hz and 0.15 Hz 3) During head-up tilt in normal subjects The time-evolution of the cardiovascular variability during the transition from supine to standing is well known [13], [23] and can be compared to SPWVDCDM results. The subjects were recorded over two periods of five minutes, first supine, then standing at 0.25 Hz paced breathing. 4) During autonomic blockade in normal subjects The cardiovascular variability is greatly reduced by a total autonomic blockade [19]. The subjects, under atropine and bisopropol administration, were recorded over a period of thirty minutes at 0.25-Hz paced breathing. 3) Signal Processing: The two methods were applied with the following parameters.

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Fig. 3. (a)Estimation of the HF instantaneous parameters with CDM and SPWVD on the x (k ). (b) x (k ) time series. Dotted lines stand for real IAmp and IF values, continuous lines stand for SPWVD and dashed lines for CDM results. TABLE I NUMERICAL RESULTS ON SYNTHETIC SIGNALS. eIAmp STAND FOR THE ERROR ON IAmp ESTIMATION [ms], eIF STAND FOR THE ERROR ON IF ESTIMATION [Hz], OBTAINED WITH THE TWO METHODS. THEY ARE REPRESENTED AS MEAN STANDARD DEVIATION. SEE (15), (16), AND FIG. 3

Preliminary band-pass filters: the LF band was centered on Hz, task force definition [26]) and the 0.09 Hz ( Hz) for RR-like series or HF band on 0.25 Hz ( Hz) the 0.25 Hz paced breathing, on 0.15 Hz ( Hz, for the 0.15 Hz paced breathing or on 0.25 ( Task Force definition [26]) for the spontaneous breathing. were 0.09 Hz for the LF CDM: reference frequencies for the HF band. band and the instantaneous SPWVD: frequency and time smoothing Hamming and , of 512 points and 21 points, windows respectively. III. RESULTS The joint SPWVDCDM method provides an excellent performance for each test: during periods of very low and (largely smaller than 0.03 as discussed later), correand estimates, they give identical sponding to reliable results, very close to real values in RR-like series (Fig. 3). A. Evaluation of the Instantaneous Spectral Parameters on Synthetic Signals The and falls in Fig. 3 are accompanied by an increase in corresponding to an unreliable estimate.

The noisier time series corresponds to higher and estimates, Fig. 3(b) and Table I. This increase is more visible is lower by comparing the first and the second when the part of Fig. 3(b) and by comparing the third and forth column values correspond to reliable in Table I. The same low estimate, depending on the noise level present or unreliable in the signal as shown by the left side of Fig. 3(a) and the first column in Table I and by the left side of Fig. 3(b) and the third column in Table I. CDM and SPWVD may estimate close values also with high and values. However, during estimate is unreliable as the error is large, see these periods, Fig. 3(b) and third column in Table I. B. Evaluation of the Instantaneous Spectral Parameters on Real Cardiovascular Time Series 1) HF Parameter Assessment: a) During Spontaneous and Paced Breathing in Normal and Subjects: During paced breathing, the very low values reflect the perfect concentration of the SPWVD , shown at 0.25-Hz paced breathing on Fig. 4(b). around the and estimated by CDM and SPWVD In these cases, estimethods are nearly constant in time and very close. mate corresponds exactly to the imposed respiratory rhythm

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Fig. 4. Three-dimensional time dependent spectrum in the HF band of an RR series and estimation of the instantaneous parameters, IAmp and IF, with CDM and SPWVD on an RR series in a normal subject during (a) spontaneous breathing and (b) 0.25-Hz paced breathing. Continuous lines stand for SPWVD and dashed lines for CDM results.

[Figs. 4(b), 57]. The values are higher at 0.15 Hz than , as already evidenced [2], [15]. at 0.25 Hz estimate in HF has to be During spontaneous breathing, interpreted with caution, because the signal can not be considered merely monocomponent, as shown by the three-dimensional representation of the SPWVD in Fig. 4(a). There is an higher spectral dispersion than during paced breathing, quan. Remark that the large HF band titatively described by since all the HF signal endefinition leads to a very low ergy is concentrated in this predefined frequency band. b) During Head-Up Tilt and Autonomic Blockade in Normal Subjects: With the head-up tilt test, the HF is strongly reduced when the subject is standing, as already and estimates described [13], [23]; in parallel, the are enhanced (Fig. 6). The two conditions, head-up tilt in the standing position (Fig. 6) and autonomic blockade (Fig. 7), together realized at 0.25-Hz paced breathing, show that even with and are very small, allowing a low variability, estimate in the HF band.

Fig. 5. Estimation of the HF instantaneous spectral parameters, IAmp, and IF, with CDM and SPWVD on an RR series in a normal subject during 0.15-Hz paced breathing. Continuous lines stand for SPWVD and dashed lines for CDM results.

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Fig. 6. Estimation of the HF instantaneous spectral parameters, IAmp, and IF, with CDM and SPWVD on an RR series in a normal subject during head-up tilt test and 0.25 Hz paced breathing. Continuous lines stand for SPWVD and dashed lines for CDM results.

Fig. 8. Estimation of the HF instantaneous spectral parameters, IAmp and IPh, on an SBP time series in (a) a normal subject and (b) a chronic heart failure subject during 0.15-Hz paced breathing. b1 and b2 correspond to periods with IPh shifts and IAmp falls while b3 corresponds to a period with IPh shifts without IAmp falls.

paced breathing, Fig. 9(b). Large and values well describe the spreading of the instantaneous spectra over the estimate are frequency axis. Similar results concerning the found during head-up tilt and autonomic blockade in normal subjects and even in chronic heart failure subjects, so they are not reported in the following. IV. DISCUSSION A. Joint SPWVDCDM Method The ability of the joint SPWVDCDM method to detect , and in abrupt changes in the instantaneous cardiovascular time series was validated in all tested conditions. Simulation examples. In Fig. 3, we showed that similar correspond to reliable or unreliable estilevel on mate depending on the noise present in the signal. Obviously, falls, and estimates must be diswhenever carded because the spectral component disappeared from the cardiovascular time series, examples are shown in Fig. 4(a) falls and periods b1, b2 in Fig. 8(b). In general, these and . Sometimes, however, correspond to high estimated by SPWVD does not fall contrary to CDM, because of smoothing operation, and leads to small and , as shown in Fig. 4(a). We conclude that level is useful but not sensitive enough to assess the reliability and as usually proposed [11]. This reliability is of greatly improved by the joint use of a threshold in the and indexes. Hence, the detection of reliable and estimate periods needs the use of the SPWVD method by the means of an a priori defined threshold value for and parameters. The definition of this threshold value requires a tradeoff between the desired reliability and the necessity to keep time-significant periods for statistical purposes, as already applied to real data [16]. Fig. 3 shows that this threshold must be largely smaller than 0.03, for and . Moreover, to avoid inaccuracy due both to cross-oscillatory terms present in the SPWVD we suggest

Fig. 7. Estimation of the HF instantaneous spectral parameters, IAmp, and IF, with CDM and SPWVD on an RR series in a normal subject under autonomic blockade and during 0.25-Hz paced breathing. Continuous lines stand for SPWVD and dashed lines for CDM results.

c) During Paced Breathing in Normal and Chronic Heart Failure Subjects: In control subjects, the stability of reflects the 1 : 1 coupling between breathing and the the HF component of the cardiovascular series, Fig. 8(a). In CHF is greatly reduced and presents sudden subjects, the and great falls, Fig. 8(b), corresponding to shifts in and values. In these periods, the meaningless shifts are explained by the total disappearance of the HF component in cardiovascular time series [periods b1, b2 in Fig. 8(b)]. shifts occur without falls In other periods, large and values [period b3 in Fig. 8(b)]. or high estimate is then reliable and can be interpreted: the The HF component still exists but respiratory and high frequency cardiovascular activity are desynchronized [16]. 2) LF Parameter Assessment During Spontaneous and Paced Breathing in Normal Subjects: In the LF band, the three-dimensional representation of the SPWVD does not show a clear difference between spontaneous, Fig. 9(a), and

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Fig. 9. Three-dimensional time dependent spectrum in the LF band of an RR series and estimation of the instantaneous parameters, IAmp and IF, with CDM and SPWVD on an RR series in a normal subject during (a) spontaneous breathing and (b) 0.25-Hz paced breathing. Continuous lines stand for SPWVD and dashed lines for CDM results.

TABLE II SCHEMATIC LISTING OF BEST METHOD TO ASSESS SPECTRAL INSTANTANEOUS PARAMETERS

that and must be smaller than this threshold for esat least 30 s. For example, by using this approach the timation on the left side of Fig. 3(a) will be discarded as not reliable. Clinical examples. The standing position of head-up tilt (Fig. 6) or the autonomic blockade (Fig. 7) in the HF band values combined with illustrate the case of reduced and values, allowing the and interlow pretation. On the contrary, in the LF band or in the HF band values are during spontaneous breathing, non negligible and/or values and the often combined with high

SPWVD is scattered over the frequency axis. In these cases, and interpretation is meaningless as the signal cannot be considered merely monocomponent as shown by the distributions (see Figs. 4(a) and 9). and shows that the perforThe joint use of mances are generally better in the HF than in LF band and further improved by paced breathing. In the LF band, the inand estimates should be discarded terpretation of the in many real-life situations. Conversely, in the HF band under paced breathing, even in conditions of reduced variability induced by head-up tilt, pharmacological autonomic blockade or

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autonomic disease, the joint use of and estimates. reliability of the

and

shows the

B. Estimation of the Instantaneous Spectral Parameters There is no single best method to assess the instantaneous spectral parameters in real cardiovascular time-series as this choice depends on the parameters that one wants estimate, as shown in Table II. parameter, both methods are In fact, to estimate the very reliable in every condition and in both the HF and LF bands, see Figs. 47. The CDM is preferable as the computational load required by the SPWVD is much greater. The detection of reliestimate periods requires the use of the SPWVD able and method by the means of an a priori defined threshold value and parameters, as previously described. for V. CONCLUSION SPWVD and CDM methods provide identical results on synthetic signal analysis and very close results in real cardiovascular time series in different physiological and pathological situations showing clear complementary characteristics: CDM gives a measure of the phase relationship between respiratory activity and high frequency oscillation in cardiovascular time series, not measurable by the SPWVD method. SPWVD gives useful indexes directly related to the noise present in the signal and to the interaction between the different spectral components, which are not measurable by CDM. Therefore, together they provide a reliable algorithm to assess instantaneous spectral parameters in nonstationary cardiovascular time series. REFERENCES
[1] S. Akselrod, D. Gordon, J. B. Madwed, N. C. Snidman, D. C. Shannon, and R. J. Cohen, Power spectral analysis of heart rate fluctuation: A quantitative probe of beat-to-beat cardiovascular control, Sci., vol. 213, pp. 220222, 1981. [2] A. Angelone and N. A. Coulter, Respiratory sinus arrhythmia: A frequency dependent phenomenon, J. Appl. Physiol., vol. 19, no. 3, pp. 479482, 1964. [3] P. Bloomfield, Complex demodulation, in Fourier Analysis of Time Series: An Introduction, P. Bloomfield, Ed. New York: Wiley, 1976, pp. 118150. [4] B. Boashash and P. Black, An efficient real-time implementation of the WignerVille distribution, IEEE Trans Acoust. Speech Signal Processing, vol. ASSP-35, pp. 16111618, Nov. 1987. [5] B. Boashash, Estimating and interpreting the instantaneous frequency of a signalPart 1: Fundamentals, IEEE Trans Acoust. Speech Signal Processing, vol. 80, pp. 520538, Apr. 1992. [6] , Estimating and interpreting the instantaneous frequency of a signalPart 2: Algorithms and applications, IEEE Trans Acoust. Speech Signal Processing, vol. 80, pp. 539568, Apr. 1992. [7] M. Chiollaz, B. Escudie, and A. Hellion, Une condition ncessaire et suffisante pour lcriture du modle exponentiel des signaux dnergie fini, Ann. Telecommun., vol. 33, no. 12, pp. 6970, 1978. [8] L. Cohen, Time-frequency distributionA review, Proc. IEEE, vol. 77, July 1989. [9] D. Gabor, Theory of communications, Proc. IEEE, vol. 93, pp. 429457, 1946. [10] J. Hayano, Continuos assessment of hemodynamic control by complex demodulation of cardiovascular variability, Am. J. Physiol. (Heart Circ. Physiol. 33), vol. 264, pp. H1229H1238, 1993. [11] , Assessment of frequency shifts in RR interval variability and respiration with complex demodulation, J. Appl. Physiol., vol. 77, no. 6, pp. 28792888, 1994.

[12] P. Y. Ktonas and N. Papp, Instantaneous envelope and phase extraction from real signal: Theory, implementation and an application to EEG analysis, Signal Processing, vol. 2, pp. 373385, 1980. [13] S. Jasson, C. Mdigue, P. Maison-Blanche, N. Montano, L. Meyer, C. Vermeiren, P. Mansier, P. Coumel, A. Malliani, and B. Swynghedauw, Instant power spectrum analysis of heart rate variability during orthostatic tilt using a time-/frequency-domain method, Circulation, vol. 96, no. 10, pp. 35213526, Nov. 18, 1997. [14] A. Malliani, M. Pagani, F. Lombardi, and S. Cerutti, Cardiovascular neural regulation explored in the frequency domain, Circulation, vol. 84, no. 2, pp. 482492, 1991. [15] L. Mangin, A. Monti, C. Mdigue, I. Macquin-Mavier, M. Lopes, P. Gueret, A. Castaigne, B. Swynghedauw, and P. Mansier, Altered baroreflex gain during voluntary breathing in chronic heart failure, Eur. J. Heart Failure, vol. 3, no. 2, pp. 189195, Mar. 2001. [16] L. Mangin, A. Monti, and C. Mdigue, Cardiorespiratory system dynamics in chronic heart failure, Eur. J. Heart Failure , to be published. [17] W. Martin and P. Flandrin, WignerVille spectral analysis of nonstationary processes, IEEE Trans. Acoust. Speech Signal Processing, vol. ASSP-33, pp. 14611470, Dec. 1985. [18] C. Mdigue, C. Vermeiren, M. Garrido, M. Pea, and P. Peirano, Assessment of autonomic dysfunction in iron-deficient anemic infants by cardio-respiratory demodulation, in Proc. IEEE-EMBS, Amsterdam, The Netherlands, Oct.Nov. 1996, pp. 336337. [19] C. Mdigue, A. Girard, D. Laude, A. Monti, M. Wargon, and J. L. Elghozi, Relationship between pulse interval and respiratory sinus arrhythmia: A time- and frequency-domain analysis of the effects of atropine, Pflgers Arch.Eur. J. Physiol., vol. 441, pp. 650655, 2001. [20] C. Mdigue, A. Monti, and A. Wambergue. (2002) LARY_CR: Software package for the Analysis of Cardio Vascular and Respiratory Rhythms, in the SCILAB_SCICOS environment. INRIA, France. [Online]. Available: http://www.inria.fr/rrrt/rt-0259.html [21] A. Monti, C. Mdigue, and M. Sorine. (2002) Short-term control of cardiovascular system: Modeling and signal analysis. INRIA, France. [Online]. Available: http://www.inria.fr/rrrt/rr-4427.html [22] F. Auger, P. Flandrin, O. Lemoine, and P. Gonalvs. TIME-FREQUENCY TOOLBOX for Matlab. [Online]. Available: http://wwwisis.enst.fr/Applications/tftb/iutsn.univ-nantes.fr/auger/tftb.html [23] S. Pola, A. Macerata, M. Emdin, and C. Marchesi, Estimation of the power spectral density in nonstationary cardiovascular time series: Assessing the role of the time-frequency representations (TFR), IEEE Trans. Biomed. Eng., vol. 43, pp. 4659, Jan. 1996. [24] S. J. Shin, W. N. Tapp, S. S. Reisman, and B. Natelson, Assessment of autonomic regulation of heart rate variability by the method of complex demodulation, IEEE Trans. Biomed. Eng., vol. 36, pp. 274283, Feb. 1989. , Baroreflex sensitivity assessed by complex demodulation of car[25] diovascular variability, Hypertension, vol. 29, pp. 11191125, 1997. [26] Task force of the European Society of Cardiology and the North American Society of pacing and electrophysiology, Heart rate variability: Standards of measurement, physiological interpretation, and clinical use, Circulation, vol. 93, pp. 10431065, 1996. [27] C. Vermeiren, P. Escourrou, Y. Papelier, G. Le Vey, and A. W. Przybyszewski, Assessment of the phase relationship between breathing, heart rate and blood pressure by modified complex demodulation, in Proc. 17th Int. Ann. IEEE Engineering Medicine Biology Society Conf., Montreal, Canada, 1995, pp. 943944.

Alessandro Monti was born in Como, Italy, in 1973. He received the M.S. degree in computer science and control process from the University of Como, and the Ph.D. degree in signal processing and control process with the dissertation Modeling and analysis of the rhythms in the cardiovascular and respiratory systems from the the National French Institute for Computer Sciences and Control Process, INRIA, Le Chesnay, France, in 1997 and 2002, respectively. His main research activity is the modeling of the control of cardiovascular and respiratory systems. Dr. Monti received an award in applied mathematics from the Ecole Polytechnique,France, for the mathematical analysis of a model of the cardiovascular system in 1998.

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Claire Mdigue was born in Angers, France, in 1953. She received the M.D. degree from the Medical Faculty of Angers, Paris, France, with specialization in parasitology and infectious diseases in 1978. After some practice in Africa, she followed the Centre National des Arts et Mtiers (CNAM) degree course, Versailles, France, in computer sciences, from 1985 to 1987. She has worked at INRIA, the National French Institute for Computer Sciences and Control Process since 1987, and is currently a Research Engineer. She is involved in the signal processing of research projects dedicated to the autonomic control of the cardiovascular system.

Laurence Mangin was born in Paris, France, in 1966. She received the M.D. degree in cardiology from St. Antoine Hospital, Paris VI University, Paris, France, and the Ph.D. degree in physiology from Paris VII University, in 1996 and 2001, respectively. She was Resident in Cardiology at Groupe Hospitalier Pitie-Salpetriere, Rennes and Paris, France. She worked in the Heart Failure and Genetic Laboratory, Pitie-Salpetriere Hospital, Paris VI University, from 1995 to 1996. She was Assistant Professor in Clinical Pharmacology from 1998 to 2000, at the Henri Mondor Hospital, Paris XII University. She was working in the Pneumology Department and the Cardiorespiratory Physiology Laboratory, Groupe Hospitalier Pitie-Salpetriere, Paris VI University, from 2000 to 2002. She is currently a Postdoctoral Fellow in the Centre for Nonlinear dynamics in Physiology and Medicine, Mc Gill University, Montreal, PQ, Canada.